Studies on the total synthesis of the glycopeptide antibiotics vancomycin, teicoplanin, chloropeptins, RP-66453, ramoplanin, and their key partial structures, analogs, and analog libraries are detailed. Their comparative examination may shed further light on the subtle aspects of their site and mechanism of action, identify the role and importance of their structural features, probe engineered structural changes introduced to address the emerging clinical resistance (binding to L-Lys-D-Ala-D-Lac vs L-Lys-D- Ala-D-Ala), and should identify simpler structures with improved properties. Similarly, details of proposed total syntheses of thiocoraline and BE-22179, C2- symmetric cyclic octadepsipeptides possessing two pendant heterocyclic chromophores which are related to sandramycin, the luzopeptins, and quinoxapeptins and which derive their properties through sequence selective DNA bisintercalation, are presented. The definition of the DNA binding properties and biological properties of thiocoraline and BE-22179, key partial structures, and analogs will be conducted as will be a continuation of analogous studies on the luzopeptins and quinoxapeptins. Additionally, plans for the preparation of libraries of analogs of HUN-7293 are detailed to probe and optimize its structural features responsible for inhibition of cell adhesion molecule expression (VCAM-1) and the resultant anti-inflammatory activity and activity in autoimmune diseases.